GRK inhibition, cell permeability, and membrane retention of key inhibitors
Values are averages of n = 4 at pH of 7.4. Error for Pe and %R are shown as S.D. GRK2 and GRK5 IC50 values are reproduced here for ease of comparison and represent an average of three separate experiments run in duplicate. Corresponding references are provided for previously published data.
| Compound # | Avg Pe (×10−6 cm/s) | Avg %R | GRK2 IC50 (μM) | GRK5 IC50 (μM) | Reference for IC50 Data |
|---|---|---|---|---|---|
| Paroxetine | 92 ± 7 | 34 ± 2 | 1.4 | >100 | Waldschmidt et al., 2017 |
| 258748 | <0.3 | 8 ± 1 | 0.008 | 0.24 | Bouley et al., 2017 |
| 258747 | 1.2 ± 0.1 | 78 ± 1 | 0.018 | 1.5 | Table 1 |
| 258208 (14as) | 1.4 ± 0.7 | 46 ± 1 | 0.03 | 7.1 | Waldschmidt et al., 2017 |
| 224061 | 23 ± 1 | 66 ± 1 | 0.066 | 1.3 | Bouley et al., 2017 |
| 257284 | <0.5 | 29 ± 2 | 0.10 | 0.50 | Bouley et al., 2017 |
| 258002 | 18 ± 3 | 69 ± 3 | 0.14 | 3.7 | Bouley et al., 2017 |
| GSK180736A | ND | ND | 0.77 | >100 | Waldschmidt et al., 2016 |
| 224406 (12n) | ND | ND | 0.13 | >100 | Waldschmidt et al., 2016 |
| 215022 (12 h) | 0.21 ± 0.05 | 5 ± 1 | 0.15 | 0.38 | Waldschmidt et al., 2016 |
| 257142 (33) | 0.12 ± 0.01 | 6 ± 1 | 0.25 | 0.26 | Waldschmidt et al., 2018 |
| Propanolol | 79 ± 10 | 31 ± 2 | NA | NA | |
| Atenolol | <0.4 | 8 ± 1 | NA | NA |
NA, not applicable ND, not done; Pe, effective permeability; %R, percent membrane retention.